chr8-30845915-T-C

Variant names:

• chr8-30845915-T-C
• rs323346
• NM_001350162.2:c.4252A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001350162.2(TEX15):​c.4252A>G​(p.Ile1418Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 1,612,788 control chromosomes in the GnomAD database, including 50,007 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.34 (13300 hom., cov: 32)
  • Exomes 𝑓: 0.20 (36707 hom.)
• Consequence: TEX15 NM_001350162.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0880
• Publications: 33 publications found

Genes affected

TEX15 (HGNC:11738): (testis expressed 15, meiosis and synapsis associated) This gene encodes a protein that is required for DNA double-strand break repair, chromosome synapsis, and meiotic recombination in spermatocytes. Male mice with a knockout of the orthologous gene are viable but sterile. Loss-of-function mutations in the orthologous mouse gene cause early meiotic arrest in spermatocytes, before the mid-pachytene stage. Naturally occurring mutations in this gene are associated with nonobstructive azoospermia. [provided by RefSeq, Apr 2017]

TEX15 Gene-Disease associations (from GenCC):

• male infertility with azoospermia or oligozoospermia due to single gene mutation

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• spermatogenic failure 25

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.6742902E-6).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.709 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001350162.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TEX15	NM_001350162.2	MANE Select	c.4252A>G	p.Ile1418Val	missense	Exon 8 of 11	NP_001337091.1	A0A2R8Y358

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TEX15	ENST00000643185.2	MANE Select	c.4252A>G	p.Ile1418Val	missense	Exon 8 of 11	ENSP00000493555.1	A0A2R8Y358
	TEX15	ENST00000256246.5	TSL:1	c.3103A>G	p.Ile1035Val	missense	Exon 1 of 4	ENSP00000256246.2	Q9BXT5
	TEX15	ENST00000638951.1	TSL:5	c.4264A>G	p.Ile1422Val	missense	Exon 7 of 10	ENSP00000492713.1	A0A1W2PS94

Frequencies

GnomAD3 genomes AF: 0.343 AC: 52044 AN: 151710 Hom.: 13270 Cov.: 32

Gnomad AFR AF: 0.716

Gnomad AMI AF: 0.0779

Gnomad AMR AF: 0.334

Gnomad ASJ AF: 0.156

Gnomad EAS AF: 0.100

Gnomad SAS AF: 0.287

Gnomad FIN AF: 0.225

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.173

Gnomad OTH AF: 0.313

GnomAD2 exomes AF: 0.251 AC: 62818 AN: 250134 AF XY: 0.238

Gnomad AFR exome AF: 0.730

Gnomad AMR exome AF: 0.394

Gnomad ASJ exome AF: 0.150

Gnomad EAS exome AF: 0.0981

Gnomad FIN exome AF: 0.221

Gnomad NFE exome AF: 0.173

Gnomad OTH exome AF: 0.215

GnomAD4 exome AF: 0.201 AC: 294118 AN: 1460960 Hom.: 36707 Cov.: 36 AF XY: 0.200 AC XY: 145575 AN XY: 726774

African (AFR) AF: 0.732 AC: 24492 AN: 33442

American (AMR) AF: 0.389 AC: 17380 AN: 44654

Ashkenazi Jewish (ASJ) AF: 0.148 AC: 3875 AN: 26110

East Asian (EAS) AF: 0.105 AC: 4167 AN: 39672

South Asian (SAS) AF: 0.275 AC: 23664 AN: 86142

European-Finnish (FIN) AF: 0.218 AC: 11592 AN: 53296

Middle Eastern (MID) AF: 0.193 AC: 1109 AN: 5760

European-Non Finnish (NFE) AF: 0.175 AC: 194766 AN: 1111538

Other (OTH) AF: 0.217 AC: 13073 AN: 60346

GnomAD4 genome AF: 0.343 AC: 52137 AN: 151828 Hom.: 13300 Cov.: 32 AF XY: 0.343 AC XY: 25444 AN XY: 74242

African (AFR) AF: 0.716 AC: 29660 AN: 41444

American (AMR) AF: 0.335 AC: 5104 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.156 AC: 540 AN: 3464

East Asian (EAS) AF: 0.101 AC: 522 AN: 5178

South Asian (SAS) AF: 0.285 AC: 1376 AN: 4820

European-Finnish (FIN) AF: 0.225 AC: 2382 AN: 10576

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.174 AC: 11762 AN: 67790

Other (OTH) AF: 0.312 AC: 657 AN: 2104

Alfa AF: 0.216 Hom.: 22866

Bravo AF: 0.366

TwinsUK AF: 0.168 AC: 622

ALSPAC AF: 0.187 AC: 722

ESP6500AA AF: 0.694 AC: 3058

ESP6500EA AF: 0.171 AC: 1470

ExAC AF: 0.256 AC: 31124

Asia WGS AF: 0.255 AC: 888 AN: 3478

EpiCase AF: 0.162

EpiControl AF: 0.167

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.79	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	11
DANN	Benign	0.78
DEOGEN2	Benign	0.049	T
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.32
FATHMM_MKL	Benign	0.44	N
LIST_S2	Benign	0.61	T
MetaRNN	Benign	0.0000017	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.42	N
PhyloP100		0.088
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.26	N
REVEL	Benign	0.036
Sift	Benign	0.62	T
Sift4G	Benign	1.0	T
Polyphen		0.037	B
Vest4		0.048
MPC		0.026
ClinPred		0.0017	T
GERP RS		0.22
Varity_R		0.031
gMVP		0.014
Mutation Taster		=97/3	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs323346; hg19: chr8-30703431; COSMIC: COSV56351000;